Merry King was a 48-year-old special education teacher in the

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1 Stevia: sweet...but how safe? p. 9 Eat slowly, eat less, p. 8 Is chocolate a health food? p. 12 OCTOBER 2008 $2.50 CENTER FOR SCIENCE IN THE PUBLIC INTEREST Photo: Eric Erbe. Courtesy U.S. Department of Agriculture, Agricultural Research Service. Digital colorization by The Page Group. A cluster of E. coli. Merry King was a 48-year-old special education teacher in the suburbs of Washington, DC. She first felt abdominal pain on December 1, 2007, according to The Washington Post. A doctor in a local emergency room, suspecting that ovarian cysts were to blame, sent her home with painkillers. Though she was later hospitalized, King died of methicillin-resistant Staphylococcus aureus, also known as MRSA, on December 9. Invasive MRSA infections strike roughly 94,000 people in the United States each year, according to the Centers for Disease Control and Prevention. An estimated 18,650 of them die, more than the number who die each year of AIDS. It s not just Staph. Physicians are finding resistant strains of E. coli, E. faecium, Klebsiella, Acinetobacter, Pseudomonas, and other bacteria. And hospitals are no longer the only place they strike. The more we use antibiotics to treat illness and to raise animals for food the closer we come to ravaging infections that the miracle drugs are powerless to treat. Continued on page 3.

2 COVER STORY J. Glenn Morris, Jr., is an internationally recognized public health scientist and physician who directs the University of Florida s Emerging Pathogens Institute. He began his career at the Centers for Disease Control, has served on four National Academy of Sciences food safety committees, and was part of a U.S. Department of Agriculture team that helped rewrite the nation s food inspection regulations. Morris is a member of Nutrition Action s scientific advisory board. He spoke to NAH s Bonnie Liebman by phone from Gainesville. According to news reports, U.S. Marine Jonathan Gadsden died of a resistant Acinetobacter baumanii infection a month after surviving lifethreatening injuries in Iraq, and Nicholas Fusco, 57, died after catching methicillin-resistant Staphylococcus aureus (MRSA) and vancomycinresistant Enterococci (VRE) while in a New Jersey hospital for minor abdominal surgery. No one knows how 39-year-old Robert Sweitzer of Tucson, Arizona, got the MRSA that killed him. And bacteria are spreading beyond the hospital. In June, researchers at the University of Iowa found MRSA in 70 percent of the pigs on 10 farms in Iowa and Illinois and in 45 percent of the workers on those farms. Although cooking kills the bacteria, anyone who touches the raw meat could easily end up with an infection. And odds are that it won t be long before most Staph is resistant Staph. Here s what you can do to prevent the spread of bacteria that are immune to antibiotics. Illustration: Adapted from National Institute of Allergy and Infectious Diseases. Q: What is antibiotic resistance? A: It s the ability of microorganisms to protect themselves or to fight off the effects of antibiotics, which are compounds that kill bacteria. As a normal part of life, bacteria evolve to sidestep the mechanisms by which antibiotics can kill them. Q: So medicines no longer work? A: Right. Bacteria are constantly evolving and changing so as to better survive in their environments. Since the beginning of the antibiotic era, we have used increasing amounts of antibiotics with the intent of killing off harmful bacteria. But that has driven the evolutionary process so that it s become highly advantageous to the bacteria that have the genes for resistance, because they can live and all the others die. [See Survival of the Fittest. ] Q: So antibiotics don t last forever? A: True. We now recognize that with enough time, antibiotic resistance will emerge in virtually every instance. It s not whether but when strains will become resistant to specific antibiotics. So we have a window during which an antibiotic has the ability to kill certain classes of bacteria. But ultimately, the bacteria are going to mutate and continue to grow despite the antibiotic. Non-resistant bacteria exist Mutation in DNA survival of the fittest Bacteria multiply by the billions A few of these bacteria will mutate. Q: Many people don t remember a time when infections were lethal? A: Right. Much of modern medicine is based on the assumption that we can quickly and effectively kill any bacteria that are causing infections. That understanding has begun to change as bacteria > > > > > Some mutations make the bacteria In the presence of antibiotics, only bacteria survive. resistant bacteria multiply and thrive When people take antibiotics, they wipe out the bacteria that have no mutations, which leaves the resistant bacteria to thrive. NUTRITION ACTION HEALTHLETTER OCTOBER

3 COVER STORY Illustration: Adapted from National Institute of Allergy and Infectious Diseases. have become increasingly resistant to antibiotics. s are treasures. We need to use them in a way that minimizes the chance or the speed with which resistance will develop. Beyond MRSA Q: Which resistant bugs are spreading? A: Methicillin-resistant Staphylococcus aureus, or MRSA, probably has received the most recent attention. It has been a cause of serious infections in hospitals for many years, but only recently has spread into the community, causing infections in people who have not had any contact with hospitals. It is of particular concern because many of the strains being seen in patients outside of hospitals appear to have increased potential for virulence that is, for causing disease. Q: And it s not just Staph? A: Right. Resistance is growing among a number of different organisms in hospitals like Enterococcus, Klebsiella, Acinetobacter, Pseudomonas, and Enterobacter that most people aren t familiar with. It s an ongoing problem in hospitals, where bacteria are developing increasing levels of resistance, because that s where we use the most antibiotics. But with MRSA, and potentially with other bacteria like Pneumococci, we are beginning to see resistant microorganisms outside hospitals. Q: Why? A: One reason is the increasing movement of patients out of hospitals and back into the community. It used to be that you d come in and stay in the hospital for a week. Now you come in and you re there for three hours and they kick you out. That has increased the antibiotic use in the community and put sicker patients back into the community. And physicians outside of hospitals are Resistant and non-resistant bacteria exist Non- Resistant Bacterium Q: So they ask for antibiotics? A: Yes. But antibiotics are only good for bacterial infections. They don t help for the majority of upper respiratory infections, which are caused by viruses. We ve been trying very hard to educate physi- - Resistant Bacterium prescribing antibiotics more often, so we have more resistance everywhere. It s a major concern. How Bacteria Resist Q: How does resistance spread? A: We are awash in bacteria. We don t see them and aren t aware of them, but our world is swarming with both good and bad bacteria. They are all over everything and, in particular, they are all over us and throughout our bodies. They re in our intestinal tract, and our skin, nose, mouth. So if you get a strain of bacteria that is, it becomes fairly easy for the genetic material that causes resistance to move to the non-resistant bacteria that have taken up housekeeping right next door. Q: How? A: Bacteria are highly promiscuous. It s amazing how often bacteria are swapping off their DNA. Sometimes the genetic material moves on a plasmid, which is a strand of DNA. Sometimes it moves on jumping genes what we call transposons or integrons. [See Sex and the Single Bacterium. ] So if you bring in a strain of bacteria that has a resistance gene, and you also have a patient who may be taking an antibiotic, there s a high likelihood that those genes are going to move not only to the same species, but to other related species as well. Sex & The Single Bacterium Bacteria multiply by the billions Bacteria that have DNA may transfer a copy of these genes to other bacteria. GENE TRANSFER Non-resistant bacteria receive new DNA Non-resistant bacteria become resistant. In the presence of antibiotics, only bacteria survive. How do bacteria pass on genes to other bacteria? The genes get transferred when the bacteria conjugate with other bacteria or when a virus carries the genes from one bacterium to another. Another mechanism: when cells die and break apart, nearby bacteria can scavenge the free-floating DNA from the dead cells. Q: How can hospitals keep infections from spreading? A: Traditionally, we ve waited to do a culture until patients developed an infection, but they could have spread the organism to a dozen patients by the time we figure it out. Now there s such a high level of resistance in the community particularly of MRSA that there s a raging argument as to whether we should assume that everyone is carrying resistant organisms. If we made that assumption, everyone who came into the hospital, particularly into an intensive care unit, would be isolated until we proved that they don t have resistant organisms. Q: Does resistance spread because people travel so much? A: A significant proportion of the resistance that is being seen in foodborne pathogens is associated with overseas travel, but it s hard to know about other pathogens because we re only now starting to collect good international data. It is clear, however, that we re dealing with a global issue where there is potentially rapid movement of resistant bacteria from one part of the world to another. Bacteria are constantly changing, modifying, and recombining. So if resistant strains are introduced in the United States, we can expect those resistant strains and genes to spread. -resistant bacteria multiply and thrive In the Doctor s Office Q: How can people avoid unnecessary antibiotics? A: Many people go to their doctor with a cold or the flu and expect to walk out with a prescription for an antibiotic. If they don t get one, they feel like they ve been shortchanged. 4 NUTRITION ACTION HEALTHLETTER OCTOBER 2008

4 Illustration: Adapted from The Science Creative Quarterly, Issue Three, Sept. 07-Apr. 08 (by Fan Sozzi). cians, but we also need to educate patients to minimize antibiotic usage. We need to reduce the evolutionary pressure on bacteria to become resistant. Q: If you take antibiotics, are you more likely to get a resistant bug later? A: Yes. For example, in studies we did in Baltimore, we found that the highest rates of Pneumococci were not in the inner city, but in the rich suburbs, where kids always get taken to the doctor and always get an antibiotic. They were more likely to be carrying resistant organisms than a kid in the city who never goes to the doctor and never gets antibiotics. So yes, you should try to minimize antibiotic use. Q: Unless you really need them? A: Yes. Clearly there are times when antibiotics are wonder drugs. But sometimes it s a borderline call as to whether or not you need an antibiotic. And in those circumstances, it s better if you don t take that antibiotic because that makes it less likely that the bugs that are on and in you will become resistant. Q: In what cases do antibiotics not work? A: There s no advantage to taking antibiotics for most upper respiratory infections colds, flu. And antibiotics may not do that much for vague bronchitis or for garden variety sinus infections. We don t have strong data that antibiotics are highly effective for a whole series of infections. [See Bacterial or Viral? p. 6.] Of course in some instances antibiotics are lifesaving. So it s not that you should never take antibiotics. But ask your physician, Is this antibiotic necessary? rather than What do you mean you re not giving me an antibiotic? We need to make that switch. We need to recognize that, to the bacteria that inhabit our bodies, the amount of antibiotics that we use makes a difference. Q: Are antibacterial soaps a problem? A: They may be increasing resistance, but it s controversial. Many people have this vision that bacteria are few and far between like roaches. Let s spray and get rid of them. Genes on a plasmid (chain of DNA) give bacteria at least three ways to resist antibiotics. The bugs can chop up the antibiotic, alter it, or simply pump it out of the cell. pump it out alter it CUT IT UP Simply ResistiblE -degrading enzyme -altering enzyme Plasmid Plasmid resistance gene Plasmid resistance gene resistance gene The reality is that you re never going to get rid of bacteria, and you don t want to. Our bodies are covered with good bacteria, and it s becoming increasingly apparent that one of our strongest defenses against infection is a group of good bacteria that don t have antibiotic resistance and don t have nasty virulence genes. Q: Why do we need those bacteria? A: We want them happily enveloping our entire body our intestinal tract and our nose and mouth so when a bad bug does come along, it doesn t have any place to live because the good guys kick it out. When you take antibiotics that kill off the normal bacteria, there s a vacuum. So you open the door for fairly nasty bacteria that carry resistance genes to move in. Efflux pump That s not a good thing. What you want are normal, happy, friendly, innocuous bacteria everywhere in and on your body. New Drugs Q: Can we expect new antibiotics to solve the problem? A: We don t have many good antibiotics coming down the pipeline. We re moving toward the potential perfect storm, where we have no new antibiotics combined with increasing levels of resistance in microorganisms. We see an inexorable increase in resistance levels, and it s been very difficult to slow it down. Q: And companies won t work on new drugs if doctors try to use them only rarely? A: That s the problem. Drug companies have moved away from antibiotics because it s a low-profit area. It costs a tremendous amount of money to bring an antibiotic to market. Yet if the antibiotic works, a patient may only take it for 3 to 7 days and may never take it again. Compare that with a drug for hypertension or cholesterol, which a large chunk of the population takes on a daily basis. There you have a vast market and a lot of money flowing in. In contrast, people take a much smaller amount of antibiotic. And there are so many antibiotics that the market share for a new one is going to be minimal. From a purely financial standpoint, developing antibiotics makes no sense whatsoever. Somehow, we need to figure out a way to create the necessary financial incentives so that new antibiotics continue to be produced. If we don t, we re going to be in major trouble. Q: Are scientists working on new antibiotics to fight bioweapons? A: Yes, but it s unclear how much impact that s going to have because the research has focused on particularly dangerous pathogens like anthrax or plague or smallpox that hopefully you will never encounter. > > > > > NUTRITION ACTION HEALTHLETTER OCTOBER

5 Animals Q: Why are antibiotics used on farms? A: They are used as a growth enhancer at the subtherapeutic level that is, at lower doses than you would use to treat an infection. Low doses are particularly good at selecting for resistant strains. What I mean is that heavy doses kill off all the bacteria, including those that have developed weak resistance. In contrast, subtherapeutic doses may not be strong enough to kill off the weakly resistant ones, opening up the opportunity for further evolutionary changes and gene exchange. Q: How do you know that antibiotic resistance occurs on farms? A: We looked at a confined animal feeding operation that used tetracycline at subtherapeutic levels to enhance growth. It was an environment where there was constant antibiotic pressure. When we sampled all across the farm soil and water and all through the farm environment we found that the resistance genes for tetracycline had permeated the entire bacterial community. Everything was tetracycline-resistant. And the bacteria carried between four and five genes that made them resistant to tetracycline. We see the potential for the same thing in humans. When there is long-term use, or even short-term use, of an antibiotic, you see the evolution and transfer of antibiotic resistance genes from one species or strain to another. COVER STORY Q: How do resistant bacteria from the farm reach people? A: It works at two levels. You could touch raw chicken and then a raw food like salad or eat some undercooked chicken and became infected with a foodborne pathogen such as a resistant Campylobacter or Salmonella. If so, the antibiotics used to treat those infections may not work. That s of concern, but it s a straightforward process. What s much more complicated is that ordinary food may not carry diseasecausing bacteria, but it s still covered with Enterococci and other harmless bacteria. And those bacteria may carry resistance genes that they picked up in the farm environment. Q: Because there are so many antibiotics on the farm? A: Right. And if those bacteria are ingested or come into contact with humans, their resistance genes may transfer to harmless bacteria that live in our bodies. Bacterial or Viral? Should you see a doctor when you get a bad cold, cough, or sore throat? Before you decide, remember that cold symptoms typically last 7 to 11 days. Don t be surprised if a cough or runny nose lasts 2 weeks. Doctors often start to worry about pneumonia if a cough lasts more than 3 weeks (and when patients have other symptoms). Sometimes, you just have to wait it out. Bacterial infections cause Some ear infections Severe sinus infections Strep throat Urinary tract infections Many wound and skin infections Source: Viral infections cause Most ear infections Colds Influenza (flu) Most coughs Most sore throats Bronchitis Stomach flu (viral gastroenteritis) Q: So the bugs that cause urinary tract infections may pick up the resistance genes from normal bugs? A: Exactly. Several years ago, a very interesting study looked at a particularly nasty strain of E. coli that causes UTIs. The investigators thought that this strain was spreading so rapidly on a national level because it had a foodborne origin. That would explain how it might spread in multiple communities across the country. We tend to think about discrete diseases, like a urinary tract infection or a foodborne disease infection. But in reality, UTIs generally arise from bacteria that are present in your intestinal tract. The bacteria in your intestinal tract may come from food or may be influenced by the bacteria that you ingest. Q: Do farms cause more resistance than hospitals? A: We don t know. Even though there s a much higher likelihood that you re going to get a resistant organism in the hospital, not that many people go into hospitals. It s a relatively rare event. However, there is enough food consumed that in some mathematical models we ve created, the risk of acquiring resistance from the farm environment works out as a significantly greater risk than the hospital environment. Portions of the industry have stopped using antibiotics, particularly with the movement toward organic foods. But we still do not have good national data on the amount that is used, so it s difficult to know what proportion is attributable to agriculture vs. human therapeutics. Q: Some people say that 70 percent goes to agriculture. A: That s one estimate. The industry says it s closer to 10 or 20 percent. Somewhere in the middle is the truth. The reality is that the government does not have the authority to get production figures from drug companies. So we have no way of knowing what the usage rates are. Q: Why doesn t the food industry stop using antibiotics? A: In many parts of the food industry, profit margins are razor thin. Companies claim that antibiotics can make the difference between bankruptcy and success. In contrast, Europe has moved away from antibiotics. But as the industry here points out, Europe works on a much smaller scale. The food industry feels that Europe can afford to do it, but we don t have that luxury to stop in such a cutthroat business. Q: How should it be done? A: We need a national goal to reduce the overall antibiotic use in hospitals, outside of hospitals, and in agriculture. I would like to see us move toward the European model, where there is minimal subtherapeutic antibiotic use in food agriculture. Q: Are some companies doing that? A: A number have dropped back from the subtherapeutic use of antibiotics as a growth enhancer. My impression is that it s still widespread. Until we can get good data, there is no way we can find out what s going on. 6 NUTRITION ACTION HEALTHLETTER OCTOBER 2008

6 COVER STORY Off Their Meds? In recent years, under pressure by health activists and the medical community to protect antibiotics, a growing number of companies have promised to cut back on the drugs. (We say promise because no one tests the animals feed to make sure that it s antibioticfree.) Here we list companies that claim on their labels or Web sites to use no antibiotics, even to treat illness. Any certified organic meat or poultry also fits into this category ( No antibiotics ever ). Companies in the second list ( No antibiotics, except to treat illness ) say that they don t use the drugs to make animals grow faster or to keep illness from spreading. Foster Farms, for example, says that only roughly 1% of its chickens get treated with antibiotics. Tyson, the nation s largest poultry producer, says that it sells the few chickens that are treated with antibiotics (again, about 1%) to food service operations, not to grocery stores. However, Tyson like nearly all poultry producers does start with eggs that have been injected with antibiotics before they hatch. In fact, even organic chickens often come from antibiotic-injected eggs. Apparently, it s tough to find eggs that aren t injected. (That s one reason why the U.S. Department of Agriculture s definition of organic starts when the chicken is two days old.) And Tyson (and most other chicken producers) sometimes give their animals a class of anti-microbial drugs called ionophores. They are used primarily to kill protozoa and aren t used in people, so there is little worry that they will lead to antibiotic resistance. Despite those quibbles, chicken companies deserve credit. Poultry producers have cut back in the last five years or so, says Rebecca Goldburg, senior scientist at the Environmental Defense Fund in New York. Pork is the biggest problem now. If you want to know whether your meat or chicken is raised with antibiotics, ask the company. Just listen carefully to the answer. If the company boasts that it doesn t use fluoroquinolones, for example, don t be impressed. The FDA banned fluoroquinolones a class of antibiotics that includes Cipro in chicken feed in (The FDA proposed a ban in 2000, but Bayer Corporation launched a lengthy battle that delayed the ban by nearly five years.) What led the FDA to act? Up to 80 percent of broiler chickens in some supermarkets are contaminated with Campylobacter bacteria, and fluoroquinoloneresistant strains were making people sick. By 2002, one in five Campylobacter infections was resistant. Breaking the Drug Habit Here s a sampling of companies that have cut back or cut out antibiotics. No antibiotics ever Any organic meat or poultry Bell & Evans chicken Cargill Good Nature pork Chipotle chicken, beef, pork Coleman Natural Laura s Lean Beef Murray s Chicken Nature Select chicken Panera chicken (except soups, Chicken Salad Sandwich, and Frontega Chicken Panini) Wegman s Food You Feel Good About beef, chicken, pork Whole Foods Wild Oats No antibiotics, except to treat illness Foster Farms chicken Tyson chicken NUTRITION ACTION HEALTHLETTER OCTOBER